title: Early, time-dependent disturbances of hippocampal synaptic transmission and plasticity after in utero immune challenge.
abstract: BACKGROUND
  Maternal infection during pregnancy is a recognized risk factor for the occurrence of a broad spectrum of psychiatric and neurologic disorders, including schizophrenia, autism, and cerebral palsy. Prenatal exposure of rats to lipopolysaccharide (LPS) leads to impaired learning and psychotic-like behavior in mature offspring, together with an enduring modification of glutamatergic excitatory synaptic transmission. The question that arises is whether any alterations of excitatory transmission and plasticity occurred at early developmental stages after in utero LPS exposure.
  
  
  METHODS
  Electrophysiological experiments were carried out on the CA1 area of hippocampal slices from prenatally LPS-exposed male offspring from 4 to 190 days old to study the developmental profiles of long-term depression (LTD) triggered by delivering 900 shocks either single- or paired-pulse (50-msec interval) at 1 Hz and the N-methyl-D-aspartate receptor (NMDAr) contribution to synaptic transmission.
  
  
  RESULTS
  The age-dependent drop of LTD is accelerated in prenatally LPS-exposed animals, and LTD is transiently converted into a slow-onset long-term potentiation between 16 and 25 days old. This long-term potentiation depends on Group I metabotropic glutamate receptors and protein kinase A activations and is independent of NMDArs. Maternal LPS challenge also leads to a rapid developmental impairment of synaptic NMDArs. This was associated with a concomitant reduced expression of GluN1, without any detectable alteration in the developmental switch of NMDAr GluN2 subunits.
  
  
  CONCLUSIONS
  Aberrant forms of synaptic plasticity can be detected at early developmental stages after prenatal LPS challenge concomitant with a clear hypo-functioning of the NMDAr in the hippocampus. This might result in later-occurring brain dysfunctions.
authors.affiliation: Institut des Biomolécules Max Mousseron, Montpellier, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Escobar
authors.forename: Nadine
authors.initials: N
authors.lastname: Crouzin
authors.forename: Mélanie
authors.initials: M
authors.lastname: Cavalier
authors.forename: Julie
authors.initials: J
authors.lastname: Quentin
authors.forename: Julien
authors.initials: J
authors.lastname: Roussel
authors.forename: Fabien
authors.initials: F
authors.lastname: Lanté
authors.forename: Aline Rideau
authors.initials: AR
authors.lastname: Batista-Novais
authors.forename: Catherine
authors.initials: C
authors.lastname: Cohen-Solal
authors.forename: Marie-Céleste
authors.initials: MC
authors.lastname: De Jesus Ferreira
authors.forename: Janique
authors.initials: J
authors.lastname: Guiramand
authors.forename: Gérard
authors.initials: G
authors.lastname: Barbanel
authors.forename: Michel
authors.initials: M
authors.lastname: Vignes
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D056547:CA1 Region, Hippocampal / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology*; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018408:Patch-Clamp Techniques; D011134:Polysaccharides / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D011134:Polysaccharides; D011725:Pyridines; D016194:Receptors, N-Methyl-D-Aspartate; D014633:Valine; C121001:NR2B NMDA receptor; C056639:2-amino-5-phosphopentanoic acid; C121465:6-methyl-2-(phenylethynyl)pyridine